A novel human Kruppel-associated box (KRAB) type zinc finger protein encoding gene, ZNF304, was obtained by AU-motif-directed display and RACE. This gene, which contains a tandem AU motif in the 3' untranslated region, has an ORF 1977-bp long that codes for a putative 659 residue protein with an amino-terminal KRAB domain and 13 carboxyl-terminal C2H2 zinc finger units. The gene maps to chromosome 19q13.4, a region that contains the largest zinc finger cluster so far identified in the human genome. Structurally. ZNF304 is related to a family of repressor transcription factors. ZNF304 expression was higher in lymphoid tissues but it was also detected in the following tissues, ordered by abundance: thyroid, adrenal gland, prostate, pancreas, and skeletal muscle. Jurkat, U937, and THP1 cell lines showed a relatively low expression of ZNF304. By contrast, PBLs stimulated with PHA or PMA + ionomycin showed a biphasic expression with a sharp increase at 6 h. This induction was closely parallel to IFN-gamma expression and partially to IL-4 and IL-10. The tissue distribution and kinetics of induction suggest that ZNF304 may be involved in the regulation of lymphocyte activation. (C) 2002 Elsevier Science (USA). All rights reserved.